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Updated: May 10, 2025

Enzymatic Cascade Reactions for the Synthesis of Chiral Amino Alcohols from L-lysine
Published on: February 16, 2018
Unlocking Loop Geometric Remodeling Redirects Aldo-Keto Reductase from Substrate Promiscuity to 3-Keto-Deoxynivalenol
Bin Ma1, Jiafeng Niu1, Hao Zhu1
1College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
Abstract:
Aldo-keto reductase is responsible for the formation of nontoxic 3-epi-deoxynivalenol (3-epi-DON) from 3-keto-DON, which is an enzymatic detoxification manner to completely eliminate the toxicity of mycotoxin DON against health and environmental threats. Therefore, unlocking the facilitated substrate specificity of aldo-keto reductase for 3-keto-DON has become a critical challenge for advanced catalytic performance. In this endeavor, a loop-based engineering strategy was developed for aldo-keto reductase AKR13B3 from Devosia A6-243 to catalyze 3-keto-DON. A 31.9-fold switch from a disfavored substrate to the preferred one was produced along with a significant 37.9-fold increase in catalytic efficiency. Kinetic parameter determinations, structural analyses, and molecular simulations were employed to elucidate the molecular mechanisms underlying these enhancements in catalytic activity and substrate specificity. Overall, our work presents a feasible scheme for designing aldo-keto reductases with exceptional substrate specificity and catalytic activity, holding great promise for developing enzymatic detoxification agents.
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